AS-CMC: a pan-cancer database of alternative splicing for molecular classification of cancer

Abstract

Alternative splicing (AS) is a post-transcriptional regulation that leads to the complexity of the transcriptome. Despite the growing importance of AS in cancer research, the role of AS has not been systematically studied, especially in understanding cancer molecular classification. Herein, we analyzed the molecular subtype-specific regulation of AS using The Cancer Genome Atlas data and constructed a web-based database, named Alternative Splicing for Cancer Molecular Classification (AS-CMC). Our system harbors three analysis modules for exploring subtype-specific AS events, evaluating their phenotype association, and performing pan-cancer comparison. The number of subtype-specific AS events was found to be diverse across cancer types, and some differentially regulated AS events were recurrently found in multiple cancer types. We analyzed a subtype-specific AS in exon 11 of mitogen-activated protein kinase kinase 7 (MAP3K7) as an example of a pan-cancer AS biomarker. This AS marker showed significant association with the survival of patients with stomach adenocarcinoma. Our analysis revealed AS as an important determinant for cancer molecular classification. AS-CMC is the first web-based resource that provides a comprehensive tool to explore the biological implications of AS events, facilitating the discovery of novel AS biomarkers.

RPS24 alternative splicing is a marker of cancer progression and epithelial-mesenchymal transition

“…However, the functional consequences of these changes, especially their implications for tumorigenesis, are not yet understood. In our pan-cancer AS database 14 , RPS24 AS was significantly associated with molecular subtypes of diverse cancers, suggesting its potential involvement in tumorigenesis.…”

“…We recently developed a pan-cancer database of AS events for the molecular classification of cancers (AS-CMC) 14 . Within this repository, RPS24 AS is one of the most notable AS events, displaying subtype-specific differences across multiple cancer types.…”

SpliceWiz: interactive analysis and visualization of alternative splicing in R

“…AS databases, whereby AS quantitation has been performed on large RNA-seq datasets in advance, are in growing demand. Recently, numerous AS databases have been published, covering various biological systems including diverse human and murine tissues [ 34 , 35 ], cancers [ 36–38 ] and COVID-19 [ 39 ]. SpliceWiz provides an ideal platform to create AS databases due to its ability to uniformly analyse and package data from large datasets.…”

Oncogenic Potential of Replication Factor C Subunit 4: Correlations with Tumor Progression and Assessment of Potential Inhibitors

“…These investigations have focused on discovering genes with possible association with multiple human malignancies in addition to particular tumors [ 3 ]. The ongoing advancement of cancer-related databases and bioinformatics tools has substantially improved the efficient identification of tumor markers and therapeutic targets [ 4 , 5 , 6 ]. The existing databases and technologies offer significant insights into the differential expression of genes in tumor and normal conditions and their relation to tumor stage, grade, metastasis, and clinical outcomes [ 7 ].…”